Process for the preparation of isobornylphenol

ABSTRACT

A PROCESS FOR THE PREPARATION OF ISOBORNYLPHENOLS OF THE FORMULA:   R1,R2,(ISOBORN-2-YL)-PHENOL   IN WHICH R1 AND R2 MAY BE IDENTICAL OR DIFFERENT AND EACH REPRESENT A HYDROGEN OR HALOGEN ATOM OR A STRAIGHT OR BRANCHED CHAIN LOWER ALKYL GROUP, CONTAINING NOT MORE THAN 4 CARBON ATOMS, PROVIDED THAT R1 AND R2 ARE NOT SIMULTANEOUSLY HYDROGEN ATOMS, WHICH PROCESS COMPRISES (A) CONDENSING CAMPHENE WITH A METHYL ETHER OF A PHENOL OF THE FORMULA: (CH3-O-),R1,R2-BENZENE TO YIELD A METHYL ETHER OF AN ISOBORNYLPHENOL OF FORMULA:   (CH3-O-),(ISOBORN-2-YL),R1,R2-BENZENE   AND (B) DEMETHYLATING THE INTERMEDIATE COMPOUND OF FORMULA III TO GIVE THE ISOBORNYLPHENOL OF FORMULA I.

United States Patent 3,833,671 PROCESS FOR THE PREPARATION OFISOBORNYLPHENOL Jean Mardiguian and Pierre Fournier, Paris, France, as-

US. Cl. 260-619 D 14 Claims ABSTRACT OF THE DISCLOSURE A process for thepreparation of isobornylphenols of the formula:

to yield a methyl ether of an isobornylphenol of formula:

III

and (b) demethylating the intermediate compound of formula III to givethe isobornylphenol of formula I.

This invention relates to isobornyl-phenols and their preparation. Thepresent invention provides a process for the preparation ofisobornylphenols of the formula:

in whichR and R may be identical or different and each represent ahydrogen or halogen atom or a straight or branched chain lower alkylgroup, containing not more than 4 carbon atoms, provided that R and Rare not 3,833,671 Patented Sept. 3, 1974 simultaneously hydrogen atoms,which process comprises (a) condensing camphene with a methyl ether of aphenol of the formula:

II in which R and R are as defined above, preferably at a temperaturebelow the melting point of the camphene, in the presence of stannicchloride as catalyst, and preferably also in the presence of an excessof the said ether of formula as the reaction solvent, to yield a methylether of an isobornylphenol of formula:

(l)C a R1 I l \V III in which R and R are as defined above, and (b)demethylating the intermediate compound of formula III to give theisobornylphenol of formula I.

The invention is particularly advantageous as applied to the preparationof 6-isobornyl-3,4-xylenol which is well known for its bacteriostaticproperties by: (a) condensing camphene with 3,4-dimethylanisole at atemperature below the melting point of the camphene, preferably atordinary temperature or at a lower temperature, more particularly at 0C., in the presence of stannic chloride as catalyst and preferably inthe presence of an excess of 3,4-dimethylanisole as the reactionsolvent, for a period of time of 24 to 48 hours, to form the methylether of 6-isobornyl-3,4-xylenol, and (b) demethylating the said methylether to give 6-isobornyl-3,4-xylenol, for example by reaction withhydrobromic acid in an anhydrous acetic acid medium at a temperatureabove 50 C.

The methyl ether of 6-isobornyl-3,4-xylenol is a new chemical compoundand as such within the scope of the invention.

The process of the invention has numerous advantages over the previouslyused process according to which camphene is directly condensed with aphenol in the presence of a Friedel-Crafts catalyst. In fact, since thetwo reagents are normally solid at ambient temperature the condensationmust in the previous process be carried out at a sufficiently hightemperature for the said reagents to be in the molten state.

New under these conditions a considerable quantity of isomers andundesirable by-products forms in addition to the desired product.Furthermore the condensation of the camphene with the phenol isincomplete. Thus not only is the yield of desired product low, but theseparation and purification of the said product furthermore provedifficult, involved and costly.

Unlike the prior art, if camphere is condensed according to the presentinvention with a methyl ether of a phenol, which is normally liquid atambient temperature and can be used also as reaction solvent, thecondensation can be carried out at a lower temperature, and theformation of isomers and by-products is limited and the completecondensation of the camphene favoured. Under the conditions of theinvention a crude product is obtained which contains at least 92% of thedesired intermediate product. The intermediate product can be obtainedin the pure state, in excellent yield, by crystallisation. However thequality of the crude product is sufficiently good for it to be usable assuch in the demethylation stage without further purification.

Furthermore, the demethylation reaction with hydrobromic acid inanhydrous acetic acid at a moderate temperature yields the desiredisobornylphenol in excellent yield together with a small amount ofisobornylalkylphenol acetate which can easily be hydrolysed in an acidmedium to give the isobornylphenol.

The invention is illustrated by the following non-limiting Example:

EXAMPLE 54.4 g. of 3,4-dimethylanisole and 27.2 g. of camphene (m.p.=47C.) are introduced into a 500 ml. flask cooled with an ice bath. Themixture is stirred with an electromagnetic stirrer. When the camphenehas dissolved, 6.4 ml. of stannic chloride are added dropwise by adropping funnel with stirring and cooling. When the addition iscomplete, the stoppered flask is placed in a refrigerator at C. for 40hours. After it has warmed up to ambient temperature, the reactionmixture is taken up in 300 ml. of petroleum ether and 50 ml. of waterare added thereto. The decanted organic layer is washed several timeswith 15% strength potassium hydroxide solution (a total of 600 ml.) andthen with water until neutral (a total of 800 ml.).

The organic phase is dried over sodium sulphate. The petroleum ether isevaporated, and the excess 3,-4-dimethylanisole is then distilled ofiunder a high vacuum. 25.1 g. of 3,4-dimethylanisole are recovered and awhite residue, weighing 53 g. (a yield of 97.5% of theory calculated onthe camphene) and containing 92% of the methyl ether of6-isobornyl-3,4-xylenol, is obtained. Crystallisation from methanolyields 39 g. of the methyl ether of 6-isobornyl-3,4-xylenol of 99.1%purity, m.p. 88 C. Yield=72%. Recrystallisation yields a very pureproduct melting at 90 C.

The methyl ether of -6-isobornyl-3,4-xylenol is soluble in ether,petroleum ether, acetone, benzene and chloroform and is insoluble inmethanol and ethanol. Its infrared spectrum shows characteristicabsorption bands at: 6.2, 6.7, 6.67, 6.87, 7.4, 8 and 11.2,u.

Percentage Analysis: Calculated for (3 1-1 0 (percent): O, 83.76; H,10.35; 0, 5.89. Found (percent): 0, 83.70; H, 10.42; 0, 5.08.

10 g. of the methyl ether of 6-isobornyl-3,4-xylenol obtained previously(m.p. 88 C.) are introduced into a 250 ml. flask equipped with astraight condenser into which dips a nitrogen inlet tube and a system ofabsorption tubes. 125 m1. of a 35% strength solution of HBr in anhydrousacetic acid is added thereto. The apparatus is degassed by a slightstream of nitrogen and the flask is then placed in a water bath at 40 C.The temperature is gradually raised to 60 C. with stirring. After onehour and 15 minutes a red solution is obtained which is kept at 160 C.for 6 hours and 30 minutes. At the end of this time demethylation ispractically complete. 93% of 6-isobornyl-3,4-xylenol and 7% of6-isobornyl-3,4 xylenol acetate form. The latter is hydrolysed asfollows: The mixture is evaporated in vacuo and the residue taken up in125 ml. of 95% ethyl alcohol and 10 ml. of con centrated hydrochloricacid. This mixture is refluxed for 3 hours and then evaporated todryness in vacuo. The residue is taken up in 100 ml. of petroleum etherand the solution washed with 0 m1. of 3% potassium hydroxide solutionand then with water until neutral. The solution in petroleum ether isdecolourised by passing it over a column of Florisil (50 g. in a columnof 28 mm. diameter). The column is eluted with 300 ml. of toluene andthe After crystallisation from 200 ml. of a mixture of water acetic acidcontaining 12.5% of water (by volume), washing the crystals with ml. of40% strength ethyl alcohol and drying in an oven at 60 C., 6.7 g. of6-isobornyl-3,4-xylenol of 99.1% purity are obtained, m.p. 94.5 C.,yield 70%. A fresh crystallisation yields 5.84 g. of very pure 6isobornyl-3,4-xylenol, m.p. 95.5 C. A crude product containing 98% of6-isobornyl-3,4- xylenol melting at 90 C. is recovered in 18% yield fromthe crystallisation mother liquors and can be purified.

What is claimed is:

1. A process for the preparation of an isobornylphenol of the formula:

a process comprises (a) condensing camphene with a methyl ether or aphenol of the formula:

B2 II in which R and R are as defined above, at a temperature not aboveambient temperature, in the presence of stannic chloride as catalyst, toyield a methyl ether of isobornylphenol of the formula:

' I l i I @111 in which R and R are as defined above, and (b)demethylating the intermediate compound of formula III to give theisobornyl-phenol of formula I.

2. A process for the preparation of 6-isobornyl-3,4- xylenol whichcomprises (a) condensing camphene with 3,4-dimethylanisole not aboveambient temperature, in the presence of stannic chloride as catalyst andin the presence of an excess of 3,4-dimethylanisole as the reactionsolvent, for a period of time of 24 to 48 hours, to form the methylether of 6-isobornyl-3,4-xylenol,and (b) demcthylating the said methylether to give 6-isobornyl-3,4-xylenol, by reaction with hydrobromic acidin any anhydrous acetic acid medium at a temperature above 50 C.

3. The process of claim 1 wherein the reaction temperature is 0 C.

4. The process of claim 1 wherein the reaction temperature is fromambient temperature to about 0 C.

5. The process of claim 1 wherein the condensation is carried in thepresence of an excess of the methyl ether of formula II as the reactionsolvent.

6. The process of claim 1 wherein the methyl ether is3,4-dimethylanisole. I

7. The process of claim 1 which comprises dissolving condensationthereof.

8. The process of claim 1 wherein a solution of the camphene and methylether of formula II is condensed, at the defined temperature.

9. The process of claim 6 wherein the methyl ether of formula III whichis obtained is the methyl ether 6-isobornyl-3,4-xylenol.

10. The process of claim 1 which comprises separating the reactionproduct from the reaction mixture.

11. The process of claim 1 which comprises separating the methyl etherof formula III in a yield of at least 92% from the condensation reactionproduct.

12. The process of claim 10 which comprises separating the isobornylphenol of formula I in a yield of at least 92%.

13. The process of claim 1 wherein there is separated be crystallizationa methyl ether of isobornylphenol of formula III from excess reactant offormula I.

14. The process of claim 1 wherein the condensation is carried out froma solution of camphene in 3,4-dimethylanisole and there is produced themethyl ether of 6-isobornyl-3,4-xylenol.

References Cited UNITED STATES PATENTS 2,320,846 6/ 1943 Borglin 260-612R FOREIGN PATENTS 535,114 1/1957 Canada 260619 '1) 1,355,165 2/1964France 260--619 D OTHER REFERENCES Kitchen, Jour. Amer. Chem. Soc., vol.70 (1948), 3608-3610.

Erman et al., Jour. Org. Chem., vol. 27 (1962), 1526- 1535.

English et al., Jour. Amer. Chem. Soc., vol. 71 (1949), 33 10-33 13.

Kryuchkova et al., Chem. Abs., vol. (1961), 22, 202-22, 203.

BERNARD HELFIN, Primary Examiner U.S. Cl. X.R.

